HBeAg seroconversion is followed mostly by normalization of ALT, decrease of HBV DNA to undetectable levels by non-proliferative assays—and to levels below 104 copies/ml with the more sensitive PCR-based assays—and cessation of liver inflammation.² This phase is referred to clinically as the ‘inactive hepatitis ‘B’ surface antigen (HBsAg) carrier state.’ Generally, the inactive carrier state has a very good prognosis and these patients may for decades, if not indefinitely, stay without active disease.^3,4 However, in some patients active liver disease endures after HBeAg seroconversion and HBeAg-negative chronic hepatitis B disease develops. In this latter group of patients, HBV variants with mutations in the pre-core and/or core region of the HBV genome prevail. This phase of the disease represents a late phase of hepatitis B infection and poses a serious challenge for patients and clinicians alike, not only because they may be more difficult to treat than HBeAg-positive CHB,⁵ but also because of their potential misdiagnosis as inactive HBsAg carriers.⁶

According to current treatment algorithm guidelines, treatment is indicated in patients with HBeAg-positive and HBeAg-negative CHB infection with active disease. Thus, treatment is not indicated in persons who are in the immune tolerant phase of the infection and in inactive HBsAg carriers.

Current Treatment Options for Chronic Hepatitis B
Six drugs are approved in the US for the treatment of CHB. These are standard and pegylated interferon, lamivudine, adefovir, entecavir, and telbivudine.

Treatment of Hepatitis ‘e’ Antigen-positive Chronic Hepatitis B
In HBeAg-positive CHB, the treatment end-point is well defined and the classical parameter of HBeAg seroconversion still holds true. HBeAg seroconversion is mostly accompanied by cessation of liver inflammation,2 as mentioned above. However, these patients should still be carefully monitored since—especially in a genotype D patient population—HBeAg-negative CHB disease may ensue. The decision about which treatment to begin—i.e. a finite treatment course with pegylated interferons versus prolonged treatment with a nucleos(t)ide analog (NA)—should be discussed with the patient, and the type of treatment the patient is going to receive should be a joint decision of the treating physician and the patient. In this context, the pros and cons of a finite treatment course with pegylated interferon versus a prolonged course with an NA (see Table 1) should be outlined to the patient.

Finite Treatment of Hepatitis ‘e’ Antigen-positive Chronic Hepatitis B
Around 30% of patients with HBeAg-positive CHB have been reported to reach the above outlined treatment end-points with standard interferons.⁷ A similar response rate has been reported for treatment with pegylated interferons of eAg-positive CHB.^8,9 However, in these studies patient populations are not directly comparable and in trials with conventional interferons patients with baseline ALT <2 x upper limits of normal (ULN) were mostly excluded. In line with this, a study comparing different doses of pegylated interferons with conventional interferon indicated a better response to pegylated interferon compared with conventional interferon.¹⁰ Patients with HBeAg seroconversion may lose HBsAg on long-term followup (50% or more at a median follow-up of nine years).^11,12 This has been mainly shown from studies performed in non-Asian countries; similar data could not be confirmed in Asian countries.^13,14 Baseline predictors of response in HBeAg-positive CHB patients treated with pegylated interferons are more or less the same as in those patients treated with conventional interferons. Thus, by multivariate analysis, both a high ALT and a low HBV DNA were independent predictors of HBeAg loss or seroconversion in two large studies.^9,15 In addition, HBV genotype was also found to be an independent predictor of response in one study.^9,16 Genotype A responds to treatment with pegylated interferon better than genotypes C and D.